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  • 1
    Electronic Resource
    Electronic Resource
    Grading of pituitary adenomas in acromegaly (1985)
    Springer
    Virchows Archiv 407 (1985), S. 83-95 
    Details
    ISSN: 1432-2307
    Keywords: Acromegaly ; Immunocytochemistry ; Pituitary adenoma ; Tumour grading
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a series of 284 adenomas from cases of acromegaly we studied major morphological variables using light microscopical techniques and compared them with immunocytochemical and clinical results. Using our semiquantitative estimations many inter-relationships were observed. We established the density of secretory granules, nuclear pleomorphism and the rate of occurrence of multinuclear tumour cells, as essential features of tumour differentiation. Mitotic activity and invasive growth patterns did not reveal clear dependences. Immunocytochemical analysis of 105 cases showed growth hormone (GH) in nearly all adenomas (98%), prolactin in 68%, and LH in 40%. The other hormones (ACTH, FSH, and TSH) were present at a much lower rate. Monohormonal GH-adenomas were found in only 29% of our cases. Many different combinations of hormone content could be demonstrated without any relationship to morphological or clinical data. From the linear correlations and advanced method of semiquantitative evaluation, the granular density of the tumour cells is the most useful variable for subclassification and grading of pituitary adenomas in acromegaly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00701331
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  • 2
    Electronic Resource
    Electronic Resource
    HGH, PRL and βHCG/βLH gene expression in clinically inactive pituitary adenomas detected by in situ hybridization (1991)
    Springer
    Virchows Archiv 418 (1991), S. 405-410 
    Details
    ISSN: 1432-2307
    Keywords: Pituitary adenoma ; In situ hybridization ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Within our surgical collection clinically inactive pituitary adenomas represent 30.7% of all pituitary tumours. To characterize their endocrine activity we studied 40 clinically inactive pituitary adenomas with in situ hybridization (ISH) using cRNA probes labelled with35S encoding growth hormone (GH), prolactin (PRL) and chorionic gonadotrophin (βHCG). No tumour was associated with clinical evidence of elevated hormone secretion. A mild hyperprolactinaemia not correlated with hormone or the mRNA content of the cells was interpreted to be incidental in 11 patients. By histological analysis, immunohistochemistry (IH) and electron microscopy the adenomas were diagnosed as small cell chromophobic (n=16) and large cell chromophobic (n=8) adenomas, and oncocytomas (n=16). Gene expression of one or more hormones was identified by ISH in 18 of 40 adenomas in few cells. GH and PRL gene expression was rare (GH mRNA in 3 of 40 tumours and PRL mRNA in 8 of 40 tumours) whereas in 14 of 40 adenomasβHCG/βLH gene expression was identified in scattered cells. Five of 40 adenomas lacking hybridization signals revealed hormones by IH. The detection of mRNA was accompanied by positive immunostaining for the respective hormones in 72%. The combination of ISH and IH reveals good evidence that the hormones are synthesized in the tumours and not taken up from the serum and stored in the cells. The two methods used together permit a more precise analysis of tumour biology than each alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01605926
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  • 3
    Electronic Resource
    Electronic Resource
    Detection of growth hormone, prolactin and human β-chorionic gonadotropin messenger RNA in growth-hormone-secreting pituitary adenomas by in situ hybridization (1991)
    Springer
    Virchows Archiv 418 (1991), S. 539-546 
    Details
    ISSN: 1432-2307
    Keywords: In situ hybridization ; Pituitary adenoma ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a series of 39 adenomas from patients with the clinical hyperfunction syndrome of acromegaly and in one from a case of prolactinoma we studied the mRNA expression of growth hormone (GH), prolactin (PRL) andβ-human chorionic gonadotropin (HCG) by using the technique of in situ hybridization (ISH). This technique allows the direct identification and localization of cells expressing mRNA and thus synthesizing the respective hormone. The aim of our study was to demonstrate the frequent co-expression of PRL mRNA and HCG mRNA in pituitary adenomas of acromegalic patients. Probes for ISH of the above-mentioned hormones were obtained by subcloning cDNA fragments into pGEM plasmids. Subsequent Sp6-polymerase catalysed in vitro transcription with35S-CTP revealed radio-labelled single-stranded antisense RNA probes [the probe forβHCG detectsβ-luteinizing hormone (βLH) simultaneously because of a sequence homology of 90%]. To localize the labelled hybrids, autoradiography was carried out. Light microscopical evaluation of the tissue sections demonstrated positive signals in all cases for GH, in 80% of cases for PRL and in 25% of cases for HCG [LH] mRNA. The comparison of mRNA content shown by ISH with immunocytochemical (ICC) hormone detection revaled that in all cases the detection of GH corresponded to GH mRNA content of the cells. For PRL and HCG [LH] positive mRNA detection (ISH) and negative hormone detection (ICC) occurred in some cases (PRL 17.5%; HCG [LH] 15%). In contrast, negative mRNA detection (ISH) and positive hormone content (ICC) was also demonstrated (PRL 5%; HCG [LH] 37.5%). The remaining adenomas showed both mRNA and the respective hormone, as well as negative ISH and ICC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01606505
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  • 4
    Electronic Resource
    Electronic Resource
    Pituitary adenomas with hyperfunction of TSH (1982)
    Springer
    Virchows Archiv 394 (1982), S. 255-267 
    Details
    ISSN: 1432-2307
    Keywords: Pituitary ; Adenoma ; TSH ; Ultrastructure ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a collection of 564 surgically removed pituitary adenomas, 4 cases were found to have had elevated TSH plasma levels. One of these tumors (case 1) could be classified as a highly differentiated mucoid TSH cell adenoma presenting histochemical reactions typical of, as well as electron microscopical features identical to, normal TSH cells. Immunoenzymatic studies failed to demonstrate TSH in the tumor cells. Two further adenomas (case 2 and 3) were similarly structured in many areas, but showed regions of poorer differentiation in which cells with distinct pleomorphism, irregular secretory granules, increased numbers of ribosomes and a well developed rough endoplasmic reticulum were present. In 10% of the tumor cells GH could be demonstrated immunoenzymatically, but there was no TSH. The fourth adenoma was an undifferentiated acidophilic adenoma showing pleomorphic cells having slight acidophil and partly mucoid granulations. The ultrastructure showed convoluted nuclei, increased numbers of free ribosomes as well as abundant rough endoplasmic reticulum and secretory granules which were different in size and number but distinctly of the TSH cell type. Immunoenzymatically, TSH was found in some cells, with GH in more cells. Endocrinologically, elevated levels of GH were measured in cases 2, 3 and 4 with LH being increased in case 1. Clinical and morphological correlations are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430669
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  • 5
    Electronic Resource
    Electronic Resource
    Electron microscopical morphometry of GH producing pituitary adenomas in comparison with normal GH cells (1987)
    Springer
    Virchows Archiv 411 (1987), S. 467-472 
    Details
    ISSN: 1432-2307
    Keywords: Pituitary adenomas ; GH cells ; Morphometry ; Ultrastrucutre
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary GH producing adenomas of patients with acromegaly (undifferentiated acidophil adenomas and well differentiated GH cell adenomas) were studied at the ultrastructural level and analysed morphometrically by the point counting method. They were compared with identically prepared GH cells of normal pituitaries from patients undergoing surgery for metastasizing cancer of the prostate. In the well differentiated GH cell adenomas significantly more points were counted on nucleoli, unorganized cytoplasm, rough endoplasmic reticulum, immature secretory granules, Golgi areas and on the plasma membranes, than in normal GH cells. Comparison of normal GH cells with tumour cells in undifferentiated acidophil adenomas demonstrated significantly larger volumes of nuclei, rough endoplasmic reticulum, Golgi fields, immature secretory granules and of the cell membranes, and also of nucleoli and of the mitochondria. Secretory granules and lysosomes were observed more frequently than in normal GH cells. In a comparison of both adenoma types, the well differentiated acidophil adenomas contained significantly larger volumes of the unorganized cytoplasm, secretory granules and of cell membranes, whereas more points were counted on the rough endoplasmic reticulum and on the mitochondria in undifferentiated acidophil adenomas. The differences between the normal GH cells and the GH cell in undifferentiated adenomas (mainly larger nucleoli, larger volumes of the rough endoplasmic reticulum and the lower volumes of secretory granules) indicate a higher secretory activity in the adenomas. The significant differences between the well differentiated and the undifferentiated adenomas (mainly the increased volumes of mitochondria and of the unorganized cytoplasm in the undifferentiated tumours) indicate a lower grade of differentiation and may be interpreted as signs of increased proliferation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735228
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  • 6
    Electronic Resource
    Electronic Resource
    Electron microscopical morphometry of well-differentiated and undifferentiated ACTH secreting adenomas in Cushing's disease and Nelson's syndrome (1991)
    Springer
    Virchows Archiv 419 (1991), S. 395-401 
    Details
    ISSN: 1432-2307
    Keywords: Pituitary ; ACTH-cell adenoma ; Morphometry ; Cushing's disease ; Nelson's syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adrenocorticotrophic hormone (ACTH)-secreting adenomas of patients with Cushing's disease (undifferentiated and well-differentiated ACTH-cell adenomas) were studied ultrastructurally and analysed morphometrically by a computer-supported quantitative image-analysing system. They were compared with identically prepared ACTH tumours (undifferentiated and well-differentiated ACTH-cell adenomas) of pituitaries from bilateral adrenalectomised patients with Nelson's syndrome. The aim of our study was to look for significant differences in ultrastructure and to evaluate these findings statistically regarding adenoma types and clinical syndromes. Clinical syndromes aside, more secretory granules and larger-sized prosecretory granules were measured in the well-differentiated ACTH-cell adenomas. The undifferentiated adenomas showed a greater content of nucleoli and prosecretory granules. Within the adenoma types, comparison of well-differentiated ACTH-cell adenomas showed that the clinical group of Cushing's disease contained larger areas of cytofilaments, whereas the clinical group of Nelson's syndrome had a larger tumour size and more lysosomes. Comparing the undifferentiated adenomas of both clinical groups the adenomas in Cushing's disease contained larger nuclei and more lysosomes, whereas the adenomas in Nelson's syndrome were larger in tumour size and contained larger prosecretory granules. Comparison of well-differentiated and undifferentiated adenomas in Cushing's disease showed more secretory granules and bigger prosecretory granules in well-differentiated adenomas whereas in undifferentiated adenomas the total area of the nuclei is larger, the nucleoli increase in number and size and the lysosomes are more frequent. Comparison of well-differentiated and undifferentiated adenomas in Nelson's syndrome demonstrated more lysosomes in well-differentiated adenomas and a larger total area of the nuclei in undifferentiated adenomas. The differences between the well-differentiated adenomas (mainly more secretory granules and larger prosecretory granules) and undifferentiated adenomas (mainly more and larger nuclei and nucleoli and more prosecretory granules) prove the clear separability between the adenoma types, not demonstrated in the literature up to now. The significant differences between adenomas in Cushing's disease (mainly more cytofilaments) and Nelson's syndrome (mainly more ribosomes and larger prosecretory granules) may be interpreted as different cell reactions due to the hypercortisolism present in Cushing's disease and lacking in Nelson's syndrome following adrenalectomy. Despite the fact that both clinical syndromes are based on the same adenoma types, indistinguishable by light microscopy, significant morphometrical findings in ultrastructure allow a clear discrimination of both clinical types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01605073
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  • 7
    Electronic Resource
    Electronic Resource
    Hypophysitis in surgical and autoptical specimens (1995)
    Springer
    Acta neuropathologica 90 (1995), S. 637-644 
    Details
    ISSN: 1432-0533
    Keywords: Key words Hypophysitis ; Pituitary abscess ; Pituitary tumor ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the clinical and histological findings of 11 cases of inflammatory anterior pituitary lesions, 8 of which were obtained during surgery and 3 of which were obtained from autopsies. Additionally, we extended the conventional classification of pituitary inflammatory disease by the new entity "secondary hypophysitis". Of the surgically obtained specimens 5 consisted of inflammatory extension into the pituitary gland out of the surrounding tissue. In all of these patients the inflammation originated from an additional tumor in the sellar region (4 craniopharyngiomas, 1 prolactinoma). These will be referred to as "secondary hypophysitis", an entity which has not yet been mentioned in the literature. Of the remaining 6 cases, 2 were granulomatous hypophysitis, 2 pituitary abscesses, 1 lymphocytic hypophysitis, and 1 showed extensive scarring of the anterior pituitary lobe due to preceeding lymphocytic hypophysitis. At histological examination the basic structure of the anterior pituitary was maintained in all cases. Relative counts of hormone-producing cells were normal. In secondary hypophysitis, the affected area was composed of fibrous tissue and granulation tissue. B and T lymphocytes were present in equal amounts. Granulomas were not found. Inflammatory infiltrates, granulation tissue and fibroses were seen in different proportions. Based on our results and three other cases reported in the literature so far, we think that the presently used classification of pituitary inflammatory diseases lacks an entity which describes a non-abscess-forming inflammation of the pituitary gland originating from an associated pathological process. Therefore, we introduced the term secondary hypophysitis to describe this fourth entity of pituitary inflammatory disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318578
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  • 8
    Electronic Resource
    Electronic Resource
    Hypophysitis in surgical and autoptical specimens (1995)
    Springer
    Acta neuropathologica 90 (1995), S. 637-644 
    Details
    ISSN: 1432-0533
    Keywords: Hypophysitis ; Pituitary abscess ; Pituitary tumor ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the clinical and histological findings of 11 cases of inflammatory anterior pituitary lesions, 8 of which were obtained during surgery and 3 of which were obtained from autopsies. Additionally, we extended the conventional classification of pituitary inflammatory disease by the new entity “secondary hypophysitis”. Of the surgically obtained specimens 5 consisted of inflammatory extension into the pituitary gland out of the surrounding tissue. In all of these patients the inflammation originated from an additional tumor in the sellar region (4 craniopharyngiomas, 1 prolactinoma). These will be referred to as “secondary hypophysitis”, an entity which has not yet been mentioned in the literature. Of the remaining 6 cases, 2 were granulomatous hypophysitis, 2 pituitary abscesses, 1 lymphocytic hypophysitis, and 1 showed extensive scarring of the anterior pituitary lobe due to preceeding lymphocytic hypophysitis. At histological examination the basic structure of the anterior pituitary was maintained in all cases. Relative counts of hormone-producing cells were normal. In secondary hypophysitis, the affected area was composed of fibrous tissue and granulation tissue. B and T lymphocytes were present in equal amounts. Granulomas were not found. Inflammatory infiltrates, granulation tissue and fibroses were seen in different proportions. Based on our results and three other cases reported in the literature so far, we think that the presently used classification of pituitary inflammatory diseases lacks an entity which describes a non-abscess-forming inflammation of the pituitary gland originating from an associated pathological process. Therefore, we introduced the term secondary hypophysitis to describe this fourth entity of pituitary inflammatory disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318578
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  • 9
    Electronic Resource
    Electronic Resource
    Recent developments in the treatment of acromegaly (1985)
    Springer
    Neurosurgical review 8 (1985), S. 167-173 
    Details
    ISSN: 1437-2320
    Keywords: Acromegaly ; dopamine agonists ; microsurgery ; perioperative GH-measurement ; radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In acromegaly the microsurgical transsphenoidal removal of the pituitary adenoma has become the most widely used method of treatment. In experienced hands, the therapeutic goal of rapid normalization of hormone excess and preservation of pituitary function can be achieved in most of the patients if the tumours are not too large. Medical treatment or radiotherapy alone, or in combination, are less successful for primary treatment. They are indispensable as alternative therapy in those patients not suitable for operation, and as additional methods after incomplete tumour removal. Large invasive adenomas still present a challenge for further improvement of therapeutic facilities. Intraoperative GH-measurements, as recently introduced by us, help to identify tumour residues and justify additional surgical exploration at higher risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01815441
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  • 10
    Electronic Resource
    Electronic Resource
    Proliferation Markers in Different Types of Clinically Non-Secreting Pituitary Adenomas (1999)
    Springer
    Pituitary 1 (1999), S. 213-220 
    Details
    ISSN: 1573-7403
    Keywords: pituitary adenomas ; immunohistology ; Ki-67 ; p53 ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 160 clinically non-secreting pituitary adenomas were examined in regard to their expression of the markers PCNA, bcl2, Ki 67 in the mib-1 modification and p53 which are still under investigation for their relevance to cell proliferation. The series contained 60 null cell adenomas, 60 oncocytomas and 40 gonadotroph adenomas. The groups that showed a definitely negative and definitely positive staining were evaluated in regard to their further characteristics such as size, invasiveness and recurrence. PCNA showed a highly represented immunostaining index throughout the groups, but not correlation between the PCNA index and an increased recurrence rate could be found. The staining for bcl2 was only rarely positive and only in a small number of cells. No correlation with the clinical data could be seen. We found a significant higher rate of staining in the invasive adenomas in the group of null cell adenomas and oncocytomas for Ki 67, especially in those adenomas expressing p53. p53 positivity was restricted to the invasive adenomas but was found only in 20% of all invasive adenomas. These data confirm in a sufficiently large series of clinically endocrine inactive pituitary adenomas, that p53 and Ki 67 immunohistology is usefull in evaluating the aggressive behavior of clinically silent pituitary adenomas. Nevertheless, negative results do not exclude clinically relevant invasive behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009933820856
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